A team from the Department of Genetics at the UB’s Faculty of Biology has discovered a new factor – a noggin-like gene – that plays a key role in controlling the pathway responsible for dorsoventral symmetry in animal phylogeny. The findings have been published in the journal Current Biology by the experts M. Dolores Molina, Ignacio Maeso, Emili Saló and Francesc Cebrià, from the UB’s Department of Genetics and Institute of Biomedicine (IBUB), and Ana Neto and José Luis Gómez-Skarmeta, from the Andalusian Centre for Developmental Biology, operated by the Spanish National Research Council (CSIC).

The planarian (Schmidtea mediterranea), a bilaterally symmetrical basal invertebrate, is a common model used in studies of cell regeneration, organogenesis, dorsoventral symmetry and stem cell regulation. The article describes a newly identified noggin-like gene in planarians that antagonizes the activity of the bone morphogenetic protein (BMP), a key factor in determining the dorsoventral axis in animal species. “We have produced the first description of noggin-like genes, factors that had not been characterized until in any animal model and which have a surprising function: they promote BMP activity, in contrast to the inhibitory action of noggin genes”, says Francesc Cebrià, who explains that, “We also show that noggin-like genes are present at all levels of the phylogenetic scale in vertebrates and invertebrates, and that they differ from noggin genes essentially due to the presence of a small amino acid insertion in the functional domain”. The study also presents the first evidence of noggin-mediated inhibition of the BMP pathway in planarians.

The paper, published in Current Biology, sheds new light on the control mechanisms of three-dimensional organization models in animal phylogeny. Emili Saló, director of the UB’s Developmental Biology and Genetics Research Group, explains that, “With the discovery of noggin-like genes, planarians have again shown their usefulness as a model for studying the preservation of biological mechanisms throughout the evolutionary process in animal species”.

The study presents other new information that sheds greater light on one of the molecular pathways that controls dorsoventral symmetry patterns in animals. As Francesc Cebrià explains, “the process of dorsoventral axis regeneration in planarians is directed by a dual organizer formed by BMP and the anti-dorsalizing morphogenetic protein ADMP, the same as the process in the development of vertebrates such as frogs of the genus Xenopus”. Cebrià highlights that, “This is the first scientific study to identify the ADMP protein in invertebrates with a function equivalent to that observed in vertebrates”, explaining, “This confirms the high degree of conservation of these mechanisms in biological evolution”.

The identification in planarians of this pathway shared with vertebrate species gives weight to the theory of an ancestral origin for control of the BMP/ADMP organizer. M. Dolores Molina, a doctoral student from the Department of Genetics and the study’s first author, explains that, “In Xenopus and planarians, this BMP/ADMP organizer has the same biological function. However, there is an inversion of the dorsoventral axis between invertebrates and vertebrates, meaning that BMP and ADMP induce ventralization in Xenopus and dorsalization in planarians”. Evidence suggests that the activation and inhibition mechanisms that control this organizer in planarians are similar to those described in Xenopus,but extensive work will be required to confirm these hypotheses.

Planarians are also a common biological model for basic research into stem cells and their potential application in regenerative medicine. Unlike the cases of other organisms, in planarians the mechanisms of morphogenesis and dorsoventral patterning remain active throughout the life span. Planarians also conserve a population of undifferentiated cells (neoblasts) that are ideal for in vivo study of the mechanisms of control and proliferation of stem cells. As Emili Saló explains, “Almost 25% of the total cell population in planarians is made up of stem cells, which are potential tumour cells, so regulation of the proliferation of these cells must be strictly controlled”. Future research will focus on more detailed study of these regulation pathways to give greater insight into cell differentiation in more complex systems.